The effects of amine-modified single-walled carbon nanotubes on the mouse microbiota

Abstract

BackgroundAmine-modified carbon nanotubes are drug delivery platforms with great potential that have not yet been applied in human clinical trials. Although modified nanotube vectors have the ability to carry multiple effectors, targeting agents, and even wrapped RNA, reports on unmodified, insoluble carbon nanotubes have highlighted inflammation in organs, including the intestine, with disruption of its resident microbiota. Disruption of the microbiota may allow for colonization by pathogenic bacteria, such as Clostridoidies difficile, stimulate immunoinfiltrates into the lamina propria or alter the absorption of therapeutics. Most proposed nanotube drugs are soluble, modified structures that are administered parenterally, and the majority of these soluble macromolecules are renally excreted; however, some are released into the bile, gaining access to the gastrointestinal tract.MethodsUsing environmentally isolated BALB/C mice in oral and intraperitoneal dosing models, high dose (3.80 or 4.25 mg/week), we administered amine-modified, soluble carbon nanotubes for 7 or 8 weeks. The general health and weight of the mice were monitored weekly, and upon killing, the diversity and content of their colonic, cecal, and ileal microbiota were assessed using shotgun 16S DNA sequencing.Results and conclusionWe show that while oral administration at suprapharmacological doses modestly altered the α- and β-diversity of the mouse microbiome, these changes did not result in observed changes in clinical end points. Intraperitoneally-dosed mice exhibited none of the toxicities assessed.

Do Engineered Nanomaterials Affect Immune Responses by Interacting With Gut Microbiota?

“…Strikingly, several studies found no significant effect of ENMs (Au, CuO, Ag and lysine-modified SWCNTs) on intestinal immunity ( 17 , 20 , 21 , 27 , 29 , 87 ). One possibility is that most ENMs may be rapidly excreted following ingestion, so few accumulate in the GIT and they are insufficient to modulate the immune responses.…”

“…Enrichment of Lactobacillus was found in these works, again highlighting the protective role of SCFA-producers in epithelium integrity and anti-inflammatory responses. Strikingly, several studies found no significant effect of ENMs (Au, CuO, Ag and lysine-modified SWCNTs) on intestinal immunity (17,20,21,27,29,87). One possibility is that most ENMs may be rapidly excreted following ingestion, so few accumulate in the GIT and they are insufficient to modulate the immune responses.…”

“…Oral gavage of TiO 2 ENMs in mice also modulated the gut microbiota, with Bacteroides and Akkermansia increased ( 22 ). Oral administration of non-metallic single-walled carbon nanotubes (SWCNTs) modestly altered the α- and β-diversity of the mouse microbiome ( 27 ). The modulation of animal gut microbiota by other ENMs is systemically summarized in recent reviews, which include nanoparticulate plastics, graphene oxide, multi-walled carbon nanotubes (MWCNT), SWCNT, Ag, ZnO, MoO 3 , MoS 2 , TiO 2 , CuO and SiO 2 ( 5 , 71 , 72 ).…”

“…In this situation, the gut microbiota can be in turn altered by the mucosal immunity. But, a considerable number of ENMs (Ag, SWCNT, CuO, TiO 2 ) are shown to alter the gut microbiota without inducing any detectable changes in intestinal immunity ( 17 , 22 , 27 , 29 ). These data suggest that ENMs may cooperate with the mucosal immunity to modulate the gut microbiota.…”

The role of carbon nanotubes in antibiotics drug delivery

“…SWCNT-Lys-NH 2 29, as shown in Scheme 7 was prepared from SWCNTs 1 and H-Lys(Boc)-OH 28 in the presence of paraformaldehyde (PFA) and TFA to afford lysine-modified SWCNTs 29, which were nontoxic and did not have the primary influence on the microbiota [26,27]. The main strategy was the covalent functionalization of SWCNTs with ciprofloxacin by spacer support to enhance the hydrophilichydrophobic stability and gain a fresh stable nano-antibiotic compound, which is biocompatible (Scheme 11).…”